Objective:To evaluate the expression of tertiary lymphoid structures (TLS) in renal tissues, and the relationship between TLS and clinicopathological changes and prognosis in idiopathic membranous nephropathy (IMN) patients.Methods:It was a single center retrospective study. The patients with IMN diagnosed by renal biopsy at Shengjing Hospital Affiliated to China Medical University from January 2018 to December 2020 were enrolled, and their clinicopathological data were collected. Immunohistochemistry was used to evaluate the expression of TLS in renal tissues. According to whether TLS expression in renal tissues was positive or not, the patients were divided into TLS-positive group and TLS-negative group, and the baseline differences in clinicopathological data between the two groups were compared. The clinical remission included complete remission and partial remission. Logistic regression analysis was used to analyze the correlation between serum phospholipase A2 receptor (PLA2R) antibody titer and positive TLS expression in renal tissues. Kaplan-Meier survival curve and log-rank test were performed to analyze the differences of proteinuria remission rates between TLS-positive and TLS-negative groups. Cox regression analysis was employed to identify the related factors of proteinuria remission. The receiver operating characteristic (ROC) curve was used to evaluate the value of TLS in predicting proteinuria remission.Results:A total of 120 IMN patients were included in this study, with age of 50.00 (40.00, 57.75) years and 78 (65.00%) males. The 24-hour urinary protein was (7.54±4.14) g, 89 (74.17%) patients were positive for serum PLA2R antibody, and the serum PLA2R antibody titer was 90.49 (48.88, 155.33) RU/ml. Immunohistochemical results showed that TLS was mainly distributed in the renal cortex glomeruli or around renal blood vessels in renal tissues. There were 43 patients in the TLS-positive group and 77 patients in the TLS-negative group. The positive rate of serum PLA2R antibody in the TLS-positive group was 83.72% (36/43). Compared with the TLS-negative group, the TLS-positive group had lower serum albumin ( t=-3.474, P<0.001) and estimated glomerular filtration rate ( Z=-2.076, P=0.045), while serum creatinine ( t=2.006, P=0.028), 24-hour urinary protein ( t=4.140, P<0.001), serum PLA2R antibody titer ( Z=4.628, P=0.001), glomerulosclerosis degree ( Z=2.403, P=0.019), and proportions of hypertension ( χ2=6.511, P=0.011), renal interstitial fibrosis ( χ2=4.088, P=0.043), renal interstitial inflammatory cell infiltration ( χ2=9.261, P=0.002), tubular atrophy ( χ2=4.936, P=0.026) and extremely high-risk of kidney disease progression ( χ2=9.352, P=0.002) were higher. Multivariate logistic regression analysis showed that serum PLA2R antibody titer was an independent factor correlated with positive TLS expression in renal tissues ( OR=1.014, 95% CI 1.007-1.021). The median follow-up time was 18.00 (95% CI 16.07-19.93) months. Kaplan-Meier survival curve showed that the proteinuria remission rate in the TLS-positive group was lower than that in the TLS-negative group (Log-rank χ2=9.339, P=0.002). Cox regression analysis showed that positive TLS expression was an independent factor correlated with proteinuria remission ( HR=0.228, 95% CI 0.177-0.297). ROC curve showed that TLS had a certain clinical predictive value for proteinuria remission ( AUC=0.703, 95% CI 0.608-0.798). Conclusions:IMN patients with positive TLS expression in renal tissues have a lower proteinuria remission rate, more severe pathological damage, and a higher risk of disease progression. TLS is expected to become a pathological marker for predicting the severity and prognosis of IMN.

Objective:To evaluate the expression of tertiary lymphoid structures (TLS) in renal tissues, and the relationship between TLS and clinicopathological changes and prognosis in idiopathic membranous nephropathy (IMN) patients.Methods:It was a single center retrospective study. The patients with IMN diagnosed by renal biopsy at Shengjing Hospital Affiliated to China Medical University from January 2018 to December 2020 were enrolled, and their clinicopathological data were collected. Immunohistochemistry was used to evaluate the expression of TLS in renal tissues. According to whether TLS expression in renal tissues was positive or not, the patients were divided into TLS-positive group and TLS-negative group, and the baseline differences in clinicopathological data between the two groups were compared. The clinical remission included complete remission and partial remission. Logistic regression analysis was used to analyze the correlation between serum phospholipase A2 receptor (PLA2R) antibody titer and positive TLS expression in renal tissues. Kaplan-Meier survival curve and log-rank test were performed to analyze the differences of proteinuria remission rates between TLS-positive and TLS-negative groups. Cox regression analysis was employed to identify the related factors of proteinuria remission. The receiver operating characteristic (ROC) curve was used to evaluate the value of TLS in predicting proteinuria remission.Results:A total of 120 IMN patients were included in this study, with age of 50.00 (40.00, 57.75) years and 78 (65.00%) males. The 24-hour urinary protein was (7.54±4.14) g, 89 (74.17%) patients were positive for serum PLA2R antibody, and the serum PLA2R antibody titer was 90.49 (48.88, 155.33) RU/ml. Immunohistochemical results showed that TLS was mainly distributed in the renal cortex glomeruli or around renal blood vessels in renal tissues. There were 43 patients in the TLS-positive group and 77 patients in the TLS-negative group. The positive rate of serum PLA2R antibody in the TLS-positive group was 83.72% (36/43). Compared with the TLS-negative group, the TLS-positive group had lower serum albumin ( t=-3.474, P<0.001) and estimated glomerular filtration rate ( Z=-2.076, P=0.045), while serum creatinine ( t=2.006, P=0.028), 24-hour urinary protein ( t=4.140, P<0.001), serum PLA2R antibody titer ( Z=4.628, P=0.001), glomerulosclerosis degree ( Z=2.403, P=0.019), and proportions of hypertension ( χ2=6.511, P=0.011), renal interstitial fibrosis ( χ2=4.088, P=0.043), renal interstitial inflammatory cell infiltration ( χ2=9.261, P=0.002), tubular atrophy ( χ2=4.936, P=0.026) and extremely high-risk of kidney disease progression ( χ2=9.352, P=0.002) were higher. Multivariate logistic regression analysis showed that serum PLA2R antibody titer was an independent factor correlated with positive TLS expression in renal tissues ( OR=1.014, 95% CI 1.007-1.021). The median follow-up time was 18.00 (95% CI 16.07-19.93) months. Kaplan-Meier survival curve showed that the proteinuria remission rate in the TLS-positive group was lower than that in the TLS-negative group (Log-rank χ2=9.339, P=0.002). Cox regression analysis showed that positive TLS expression was an independent factor correlated with proteinuria remission ( HR=0.228, 95% CI 0.177-0.297). ROC curve showed that TLS had a certain clinical predictive value for proteinuria remission ( AUC=0.703, 95% CI 0.608-0.798). Conclusions:IMN patients with positive TLS expression in renal tissues have a lower proteinuria remission rate, more severe pathological damage, and a higher risk of disease progression. TLS is expected to become a pathological marker for predicting the severity and prognosis of IMN.

AlM: To investigate the effect of C. sinensis extracts on HBx (Hepatitis B virus X protein) induced cell proliferation and extracellular matrix (ECM) accumulation and the underlying mechanism in cultured human mesangial cells (HMCs). METHODS: Human mesangial cells were stable transfected with pCMV-HBx to establish an HBx over-expression model, and a control group was transfected with an empty vector. Cell proliferation was determined by MTT assay and DNA synthesis assay. Western blotting was used to measure the expression of PI3K/Akt signaling pathway-related proteins and extracellular matrix. RESULTS: HBx transfection induced cell proliferation, matrix accumulation. HBx-transfected mesangial cells had increased activity of the PI3K/Akt pathways, and treatment with C. sinensis suppressed this effect. CONCLUSlON: C.sinensis attenuates the HBx-induced human mesangial cell proliferation and matrix production in human mesangial cells via inhibition of the PI3K/Akt pathways.

Objective To evaluate a noninvasive vessel encoded imaging for selective mapping of the flow territories of the left and right internal carotid arteries and vertebral-basilar arteries. Methods Seven volunteers [(33.5±4.1) years ; 3 men, 4 women] and 6 patients [(55.2 ± 3.2) years; 2 men,4women] were given written informed consent approved by the institutional review board before participating in the study. A pseudo-continuous tagging pulse train is modified to encode all vessels of interest. The selectivity of this method was demonstrated. Regional perfusion imaging was developed on the same arterial spin labeling sequence. Perfusion-weighted images of the selectively labeled cerebral arteries were obtained by subtraction of the labeled from control images. The CBF values of hemisphere, white matter, and gray matter of volunteers were calculated. The vessel territories on patients were compared with DSA. The low perfusion areas were compared with high signal areas on T2-FLAIR. Results High SNR maps of left carotid, right carotid, and basilar territories were generated in 8 minutes of scan time. Cerebral blood flow 100 g-1 were in agreement with data in the literature. Vessel encoded imaging in patients had a good agreement with DSA. The low perfusion areas were larger than high signal areas on T2-FLAIR. Conclusion We present a new method capable of evaluating both quantitatively and qualitatively the individual brain-feeding arteries in vivo.